The regulation of the pyruvate dehydrogenase complex in the perfused rat liver: a role for the mitochondrial monocarboxylate translocator.
The regulation of the pyruvate dehydrogenase complex in the perfused rat liver: a role for the mitochondrial monocarboxylate translocator.
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灌注大鼠肝脏中丙酮酸脱氢酶复合物的调节：线粒体单羧酸易位子的作用。
DOI：
10.1016/0003-9861(82)90586-0
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发表时间：
1982
影响因子：
3.9
通讯作者：
Olson,MS
中科院分区：
文献类型：
--
作者：
Patel,TB;Debuysere,MS;Scholz,R;Olson,MS
The regulation of the pyruvate dehydrogenase multienzyme complex was investigated in the isolated perfused rat liver. The rate of14CO2production from infused [1-14C]pyruvate was utilized as an index of the metabolic flux through the pyruvate dehydrogenase reaction. In the perfused liver infusion of β-hydroxybutyrate resulted in a substantial stimulation of the metabolic flux through the pyruvate dehydrogenase reaction at low (0.05 mm) perfusate pyruvate concentrations. At high (5 mm) pyruvate levels in the perfusion medium the decarboxylation of [1-14C]pyruvate was inhibited by β-hydroxybutyrate. The activation state of the pyruvate dehydrogenase complex during β-hydroxybutyrate infusion at a low pyruvate concentration was elevated by 74% above values obtained with pyruvate alone. The increase in the active form of the pyruvate dehydrogenase complex occurred in spite of increased tissue levels of acetyl-CoA and NADH observed in this condition. At a high pyruvate concentration infusion of β-hydroxybutyrate resulted in elevated acetyl-CoA and NADH levels and no change in the activation state of the pyruvate dehydrogenase complex. Stimulation of the metabolic flux through the pyruvate dehydrogenase reaction as a result of infusion of β-hydroxybutyrate at low perfusate pyruvate concentration was, to a certain extent, diminished by infusion of acetoacetate. The mitochondrial monocarboxylate translocator inhibitor α-cyanocinnamate was infused into a liver and the perfusate concentrations of pyruvate and β-hydroxybutyrate were adjusted so that the metabolic flux through the pyruvate dehydrogenase reaction and the rate of acetoacetate production were nearly equivalent to the control experiment [e.g., low (0.05 mm) pyruvate and 10 mmβ-hydroxybutyrate] performed in the absence of α-cyanocinnamate. In the presence of α-cyanocinnamate β-hydroxybutyrate infusion resulted in a substantial inhibition of pyruvate decarboxylation. This observation contrasts sharply with the experiment performed at the low pyruvate concentration where β-hydroxybutyrate infusion caused a stimulation of pyruvate decarboxylation. These experiments provide evidence suggesting that the stimulation of the flux through the pyruvate dehydrogenase reaction by β-hydroxybutyrate or other precursors of acetoacetate observed at low pyruvate concentrations is a result of an accelerated exchange of cytosolic pyruvate for intramitochondrially generated acetoacetate on the monocarboxylate translocator.
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